Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control

Ferreira, Mar, Mangino, M, Brumme, CJ, Zhao, ZZ, Medland, SE, Wright, MJ, Nyholt, DR, Gordon, S, Campbell, M, McEvoy, BP, Henders, A, Evans, DM, Lanchbury, JS, Pereyra, F, Walker, BD, Haas, DW, Soranzo, N, Spector, TD, de Bakker, PIW, Frazer, IH, Montgomery, GW, Martin, NG and Int HIV Controllers Study (2010) Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control. American Journal of Human Genetics, 86 1: 88-92. doi:10.1016/j.ajhg.2009.12.008


Author Ferreira, Mar
Mangino, M
Brumme, CJ
Zhao, ZZ
Medland, SE
Wright, MJ
Nyholt, DR
Gordon, S
Campbell, M
McEvoy, BP
Henders, A
Evans, DM
Lanchbury, JS
Pereyra, F
Walker, BD
Haas, DW
Soranzo, N
Spector, TD
de Bakker, PIW
Frazer, IH
Montgomery, GW
Martin, NG
Int HIV Controllers Study
Title Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2010-01-08
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2009.12.008
Volume 86
Issue 1
Start page 88
End page 92
Total pages 5
Place of publication Cambridge, MA, United States
Publisher Cell Press
Collection year 2010
Language eng
Formatted abstract
Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10-28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10-14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10-9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.
Keyword Genome-wide association
Family
Sample
Genes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 31 December 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Sun, 28 Feb 2010, 10:07:30 EST